1. Field of the Invention
The disclosure relates generally to a microplate mount system and methods of making and using the system.
2. Background Information
At the present time, existing technology utilizes various instrumentation to measure photometric properties such as color, absorbance, intensity, and photoluminescence at specific locations on a microplate surface where chemical and biological samples are associated. For example, optical readers are commonly used in biological fields such as genetic research, drug discovery, or diagnostic purpose to detect hundreds or thousands of compounds (e.g., DNA, oligonucleotides, proteins, etc.) typically deposited on a surface of a substrate (e.g. a glass slide) in an array configuration. It is well known in the art that proper alignment of the microplate holding the samples and the light beam of the optical device is necessary to perform many photometric measurements.
Similarly, to perform image analysis, devices such as optical scanners/readers and microscopes demand sample stages that provide consistent and accurate positioning of the microplate. Moreover, for imaging devices that utilize sensors, waveguide gratings or other microdevices on a sample surface of a substrate, alignment of the surface having correlation with an optical component is critical for consistent measurements.
Many photometric instruments make use of a multi-site microplate to prepare a large number of test samples. Microplates are typically rectangular structures made of glass or plastic, each having a plurality of wells for holding sample material. The plate itself is generally inexpensive, safe, sturdy, and convenient to handle. They are disposable, but can be cleaned easily and may be reused when necessary.
As chemical and biological sample size decreases and the number of samples increases on an array surface, alignment of the samples relative to the measuring instrument becomes progressively more important. Present and future drug discovery relies on a large number of test sites within an array. For example, to identify a specific protein sequence for a binding event with a certain type of receptor, a high density of samples is needed to expose the receptor to an many different permutations of proteins as possible. Therefore, the samples to be assayed are located on the surface in a multitude of discrete locations, each location containing a single sample. A standard microplate is typically about 127.76 mm in length×85.48 mm in width and may accommodate up to 96, 384 or even 1536 assays. Because of the small size and close spacing of the analyte samples, the microplate sample surface must be precisely and repeatedly aligned with respect to the measuring apparatus, thus allowing the measuring apparatus to make error-free measurements of the samples.
Systems are currently being developed to detect the binding of molecular species without adding labels. These systems utilize disposable microplates having sensors embedded at specific locations and a reader to interrogate those precise localities of the microplate. The utility of assays performed in such systems relies on making successive analytical observations interplayed between steps in the assay. This way, a true “before and after” analysis may be accomplished revealing the occurrence (or absence) of biological or chemical molecular interactions. Therefore, the repeatable and consistent alignment and/or positioning of a microplate incorporated into or onto a stage for analytical interrogation is crucial and necessitated by these newly developed systems.
Current measurement protocol requires four primary steps: (1) initial/background measurement, (2) removal of the plate (for additional assay steps), (3) reinsertion of the plate into the reader, (r) second measurement, and (5) comparison of first and second measurements. Following the placement of a microplate into an exact location, an initial measurement can be read by a photometric/optical instrument. Once the microplate is removed, and manipulation of its contents completed, examination of the microplate depends on the exact repositioning of the microplate into the reader. Therefore, the second/final measurement result can be adversely affected by the slightest change, rotational and/or translational, in microplate position between the initial and second/final measurement steps.
Corning, Inc., has developed and marketed the Epic® system, a label-free microplate based drug discovery tool. The Epic® technology is based on resonant waveguide grating (RWG) sensor technology. The RWG sensors are sensitive to the incidence angle of the interrogating optical signal, and as a result, the incidence angle of the interrogating optical signal on the RWG sensor must be adequately controlled to achieve acceptable performance of the sensor and reader system. In certain commercial Epic® systems the incidence angle can be controlled by, for example, using high precision stages and a precision plate nest, see for example, U.S. Patent Application Publication No. 2007/0020152, which is incorporated herein in its entirety by reference. While these components can provide adequate control of the interrogating optical signal incidence angle, the required stages can be costly, occupy a large physical volume, rely upon peripheral or auxiliary services, and rely upon extremely flat and stable mounting surfaces. These aspects of controlling the interrogating optical signal incidence angle can result in increased system cost and complexity.